The Clinical and Genetic Spectrum of Hypertrophic Cardiomyopathy in an Irish Population

Background: Hypertrophic cardiomyopathy (HCM) is an inherited disorder of cardiac muscle. It is identified clinically by left ventricular hypertrophy which is unexplained by secondary loading conditions. HCM is a highly heterogeneous condition and can cause left ventricular outflow tract obstruction, atrial arrhythmias and heart failure. HCM is the most common cause of sudden cardiac death in people under 35 years. In approximately 50% of cases, a genetic mutation is identified. The landscape of the condition is complex and our understanding continues to evolve. Research Aims and Methodology: A retrospective analysis of the database of a specialist cardiomyopathy clinic in a tertiary referral centre was performed. All patients with hypertrophic cardiomyopathy who carry gene mutations responsible for their HCM were selected for inclusion. Clinical, genetic and imaging data were reviewed for all subjects. We sought to characterise the genetic and molecular basis of HCM in an Irish population and investigate phenotype-genotype correlations. We aimed to highlight the genetic complexity of HCM observed in some individuals and families within our population. We performed an observational study of ECG changes in HCM to re-examine the sensitivity of the ECG as a screening tool, as we hypothesized that the rate of normal ECG in HCM patients is much higher than currently reported. For specific rare HCM aetiologies which are found in the Irish population, such as HCM caused by LAMP2 mutations, we sought to describe baseline and outcome measures in a cohort and describe key clinical issues in these rare populations. Conclusions: Hypertrophic cardiomyopathy is a complex condition with significant clinical and genetic variability. This thesis examines the landscape of HCM in an Irish population and seeks to expand on the current knowledge relating to clinical outcomes and specific disease subtypes and the reliability of the ECG as a screening tool.